Purpose: Pancreatic cancer (PC) is the fourth leading cause of cancer death in both men and women. The standard of care for patients with locally advanced PC is radiotherapy (RT) (54 Gy in 1.8-2 Gy per fraction) has shown highly variable success rates. 3-Dimensional (3D) PC organoids have shown promise for studying tumor response to drug and emerging treatments under in vitro conditions. Herein we investigated the potential for using 3D organoids to study and determine the precise RT response of in vivo PC tumors.
Methods: PC organoids were created from mouse PC tumor tissues and their micro-environment compared to that of the in vivo tumors. The organoids and in vivo PC tumors were treated with 0 Gy (control), 4 Gy, 6 Gy, and 8 Gy of radiation with a 250 kvP small animal x-ray irradiator and their growth measured for 10 days using brightfield microscopic imaging.
Results: PC organoids exhibited similar fibrotic micro-environment and molecular response (as seen by biomarker expression) as the in vivo tumors. The untreated tumor organoids and in vivo tumors both showed a growth of 6x the original size after 10 days, while no growth (1x growth) was seen for organoids and in vivo tumors treated with 8 Gy of x-ray radiation. Finally, PC organoids showed reduced growth rates of 2.8x and 2.2x following doses of 4 Gy and 6 Gy of x-rays.
Conclusion: PC organoids produced a similar micro-environment and exhibited similar growth as the in vivo tumors following treatment, and showed reduced growth in response to increasing doses of x-ray radiation, thus showing their potential for predicting in vivo tumor sensitivity to RT.
Funding Support, Disclosures, and Conflict of Interest: This research was supported by a Seed Grant from the Department of Radiation Oncology in the University of Maryland School of Medicine